The present invention relates to measuring backscatter waveforms behavior in time due to ultrasound excitement of tissue to determine tissue type or substance composition, and more particularly, to a method, and corresponding device and system thereof, using ultrasound waves for tissue substance differential excitation, that creates different scattering behavior changes when exciting different tissues or substances; and measuring the backscatter waveform behavior before, while, and/or after excitation periods, at one or more locations in the tissue, and measuring gradients of this behavior, to image the examined area and/or determine tissue types or substance composition irregularities.
There are many situations where it is necessary or desirable to identify tissue nature and substance in an organ. One example of such a situation is the identification of malignant areas within the body of a patient, where it is required to first find the exact location of suspected cancerous region for sampling, and then indicate whether the suspected location is in fact cancerous, and if so of what malignant nature. Other such situations include the ability to visualize a map of tissue types or substance composition for medical imaging purposes. Yet another example is the need for reading different substance levels within a body, such as glucose levels in the blood.
In these and other cases it is desirable to determine tissue irregularities for localizing suspected material, image tissues, or analyze the tissue substance. It is also desirable to identify, or find the probability of identification of, tissue as of known characteristics.
Present techniques known from the prior art for determining tissue type or substance include medical imaging, and tissue sampling such as a blood sample or biopsy techniques. Imaging of tissue type or substance and irregularities include technologies such as X-Ray, MRI, PET, Ultrasound, and IR imaging. X-Ray based tomography uses high energy electromagnetic radiation that is harmful to both patient and physician. This harmful effect substantially reduces the capacity of this technology to enable continues imagery. As X-Ray technology mainly measures acid levels in the examined area, it is limited to identifying desirable tissue differences where acid levels substantially differ. MRI uses high intensity magnetic fields. As such it yields very high cost of ownership. The need for very accurate magnetic field in MRI equipment substantially limits the geometry of the equipment, not enabling desirable physician interaction with the body of the patient at affordable costs. PET technology is limited in its capacity to identify desirable substance composition differences, and hence is used mainly in conjunction with other imaging techniques.
Ultrasound-diagnostics equipment mostly analyzes ultrasound waves' specular reflection; as such it is limited in its capacity to identify desirable tissue substance as sonic echo does not differentiate well enough between tissue materials. Table 1, a table of ultrasound speed and acoustic impedence for different soft tissues, taken from G. E. P. M. Van Venrooij, “Measurement of ultrasound velocity in human tissue,” Ultrasonics, October 1971, p. 240-242, shows that specular reflection coefficients, due to differences in acoustic impedance between soft tissues, are typically only a few times 10−4, or less, which is typically below the noise level.
TABLE 1Ultrasound velocity, density, characteristic impedance and reflectioncoefficient of normal brain tissue of some body fluids and brain tumorsNumber ofTmeasuringcerrorθZRSubstance[° C.]points N[ms−1][%][kgm−3][106 Nsm−3][×105]Sourcewater (not23.5201493.50.1997.411.4896—θ fromdegassed)handbook ofChemistry andPhysics 1968/69blood23.2101549.60.710361.6053Heparinisedblood24.2111556.40.310411.6219samples fromblood {close oversize brace} 22.61015701.510531.65343four differentblood22.4121565810361.6211patientsCSF24.491515310061.52447Fresh samplesCSF {close oversize brace} 25111509.50.510061.51954from threeCSF21.8111499210051.50662different patientsmeningioma19201524.20.4———After three hoursimmersion informalinemeningioma19.8201524.50.510311.5720.3After forty-eighthours immersionin formalineependymoma20181501310241.53717Formalisedastrocytoma24.9271517810791.6418samplesglioma22.3171500310261.53922glioma22.2201529.10.610211.5616Fresh samplesastrocytoma27.5411545.40.4———meningioma19.72015572———Five differentmeningioma19.72015461———slides of onemeningioma {close oversize brace} 19.72115692———tumourmeningioma19.71415482———meningioma19.71415692.5———
Advanced ultrasound techniques use other characteristics of the echo reflectance in the body, such as ultrasonic backscatter of power waves for elasticity measurement, however those too are not sufficient for clear differentiation between different tissue types or substances in the examined organs.
Arthur et al, in a talk “Change in Ultrasonic Backscattered Energy for Temperature Imaging: Factors Affecting Temperature Accuracy and Spatial Resolution in 3-D,” presented at the 32nd UITC, Alexandria, Va., May 16, 2007, describe tests they did to develop a technique for using changes in backscattered energy of ultrasound to produce 3-D temperature maps in soft tissue, in order to monitor hyperthermia cancer treatment. The authors calculate theoretically that the standard deviation in backscattering energy, from place to place in a liver tissue sample with many small inclusions of aqueous or lipid material, increases monotonically with temperature, and they present in vitro test results with samples of bovine liver, turkey breast, and pork muscle, that confirm their calculations. They predict that it should be possible to use this technique to measure temperature to within 0.5 degrees Celsius, with a spatial resolution of 1 cm, for some kinds of tissue, if the tissue is calibrated.
Seip and Ebbini, “Noninvasive Estimation of Tissue Temperature Response to Heating Fields Using Diagnostic Ultrasound,” IEEE Transactions on Biomedical Engineering, vol 42, pp. 828-839 (1995), describe another technique for using backscattering of diagnostic ultrasound to monitor temperature changes in tissue. The technique is based on the observation that most biological tissues are semi-regular scattering lattices. Muscle tissue, for example, may have a semi-regular lattice structure due to individual muscle fibers, with spacing on the order of 1 mm. These lattice structures produce harmonics in the backscattered ultrasound, with the frequency shift of the harmonics depending on temperature, through the temperature dependence of the sound speed, and the thermal expansion of the lattice structure. If the temperature dependence of the sound speed, and the thermal expansion coefficient, are known for the type of tissue being tested, then changes in the frequency shift can be used to measure changes in temperature. Autoregressive model-based methods are used to estimate the frequency shift. The authors state that temperature can be measured, using this technique, to within 0.4 degrees Celsius, with a spatial resolution of 1 mm. To achieve this precision, the lattice spacing, the temperature dependence of sound speed, and the thermal expansion coefficient of the tissue must all be known a priori. However, the technique could still be used to measure a relative temperature response, even if the temperature dependence of sound speed and the thermal expansion coefficient of the tissue are not known very accurately.
IR imagery is used to map the tissue's natural heat superficially, however due to the mammal natural heat control mechanisms, temperature is equalized by in-vivo tissues as heat conduction and convection occur within the organ, hence this technology is very limited in its capacity to identify desirable tissue substance.
Other means of identifying tissue substance composition include sampling tissue out of the organ for analysis. These include blood samples, biopsy, and others. The limitation of such technologies is in the need to sample out tissue from the organs, sometimes without knowing whether the sample is taken from the correct position inside the organ. Other limitations are the required handling, and the fact it is analyzed out of the living organ after loosing some of its characteristics. These currently available techniques from the prior art hence enable less than desirable functionality of real time imaging/identification or differentiation of in-vivo tissue. In particular, X-Ray harmful effects could be substantially reduced if there was to exist a harmless method for imaging in-vivo tissue at high resolution, with flexible equipment geometry, at affordable costs. Additionally, it would be preferable if there was to exist a method and system for imaging of tissue that could substantially differentiate between different tissues in an organ, and enable the identification of malignant tumors, or other irregularities in live tissue.
Blood sampling techniques known form the prior art are based on drawing of blood from the body and lack the ability of identifying the point in time where glucose levels non-linearly change from acceptable levels. In particular, the identification of time of change, could be significantly enhanced if there was to exist a capacity to conduct on going monitoring of the glucose level with non-intrusive means.